Objectives: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice. Background: Major advances in PCI techniques have considerably reduced the incidence of post-procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers. Methods: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high-volume angioplasty centers. On the basis of pre-specified clinical and PCI-linked criteria, 220 patients were selected for ambulatory PCI. Results: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4-6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non-cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non-procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10−6). Conclusions: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization. © 2012 Wiley Periodicals, Inc.